This review assessed the effects of granulocyte colony-stimulating factors (G-CSF) for diabetic foot infections. The authors concluded that G-CSF treatment does not appear to speed up resolution of diabetic foot infections, but does reduce amputations and other surgical procedures. This was generally a well-conducted review and the authors' conclusions are likely to be robust.

Authors' objectives

To assess the effects of granulocyte colony-stimulating factors (G-CSF) as adjunctive therapy for diabetic foot infections.

Searching

MEDLINE, EMBASE, LookSmart Find Articles and the Cochrane Library were searched from 1990 to July 2003; the search terms were reported. In addition, searches of diabetic foot online websites, published biographies, reference lists of retrieved articles and meeting abstracts were also conducted. Authors of primary studies and experts in the field were contacted for additional published and unpublished studies.

Study selection

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) were eligible for inclusion.

Specific interventions included in the review

Studies that compared standard treatments plus G-CSF with standard treatment alone were eligible for inclusion. Most of the included studies used filgrastim; one study used lenograstim. Most studies gave G-CSF subcutaneously; one study administered it intravenously. The duration of treatment ranged from 3 to 21 days. The included studies generally gave initial antibiotic therapy intravenously; the regimens and duration of antibiotic therapy varied.

Outcomes assessed in the review

The primary review outcome was the resolution of infection or the healing of wounds. Duration of antibiotic therapy, need for amputation, overall need for invasive interventions (including amputation, extensive debridement, angioplasty and other vascular surgery), changes in blood leukocyte count and adverse effects were also assessed.

How were decisions on the relevance of primary studies made?

The authors did not state how the studies were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

Validity was assessed and scored using the Jadad scale, which considers the reporting and handling of randomisation, blinding and handling of withdrawals. The maximum possible score was 5 points. The authors did not state who performed the validity assessment.

Data extraction

Two reviewers independently extracted the data and resolved any disagreements through discussion. The authors of studies with incomplete or missing data were contacted for additional information. Data on outcomes were extracted and used to calculate risk ratios (RRs) with 95% confidence intervals (CIs).

Methods of synthesis

How were the studies combined?

In the absence of significant heterogeneity, pooled RRs with 95% CIs were calculated for dichotomous data using the fixed-effect method of Mantel-Haenszel. The number (of patients)-needed-to-treat (NNT) to prevent one event was also calculated. Pooled weighted mean differences (WMDs) with 95% CIs were calculated for continuous data. Publication bias was assessed using a funnel plot and tested using a rank correlation test (Begg and Mazumdar) and regression asymmetry test (Egger).

How were differences between studies investigated?

Statistical heterogeneity was assessed using Cochran's Q-test and the I-squared statistic. Differences between the studies were also discussed with respect to interventions and clinical characteristics of the patients.

Results of the review

Five RCTs (n=167) were included in the review.

The studies were considered to be of reasonable quality (mean Jadad score 3.4, range: 1 to 5), with 4 studies scoring 3 or more.

No statistically significant differences between G-CSF and control were found for clinical resolution of infection, healing of wounds or the rates of wound healing.

Treatment with adjunctive G-CSF does not appear to speed up the resolution of diabetic foot infections, but it does reduce amputations and other surgical procedures.

CRD commentary

The review addressed a clear question that was defined in terms of the participants, intervention, outcomes and study design. Several relevant sources were searched and attempts were made to locate unpublished studies, thus limiting the possibility of publication bias. Appropriate methods were used to assess the presence of publication bias, but no evidence of it was found. It was unclear whether any language limitations had been applied. Methods were used to minimise the likelihood of reviewer error and bias in the extraction of data, but it was unclear whether similar steps were taken in the study selection and validity assessment processes. Validity was assessed using specified established criteria and there was adequate information about the included studies. Clinical heterogeneity among studies was discussed and statistical heterogeneity was assessed. The studies were appropriately combined in a meta-analysis. This was generally a well-conducted review and the authors' conclusions are likely to be robust.

Implications of the review for practice and research

Practice: The authors stated that the use of G-CSF should be considered as an adjunct to standard care for diabetic patients with foot infection, especially for patients with limb-threatening infections.

Research: The authors did not state any implications for further research.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.